Immune to Cancer: The CRI Blog



How CRI is Taking on Pancreatic Cancer, “The Silent Killer” 

Immunotherapy holds the greatest promise for optimizing outcomes for cancer patients, and eventually finding a cure for all cancers. Some cancers like bladder, and head and neck cancers, are more easily treatable with immunotherapy – particularly when they are caught in the early stages. Unfortunately, some other cancers do not respond nearly as well to even the most cutting-edge, currently approved treatments. Pancreatic cancer is one such cancer, and immunologists are furiously working to meet treatment demands on behalf of patients and their families. 

A Cancer with Unsettling Statistics 

The pancreas is an organ in the digestive system that sits behind the stomach while bordering the small intestine and spleen. It serves two purposes: to release insulin and glucagon into the bloodstream and to produce digestive enzymes that are distributed into the small intestine. Sadly, the frequency of pancreatic cancer diagnoses is rising, and the number of new cases and deaths is likely to more than double by 2030.  

There are several factors that create an urgent atmosphere for immunologists to come up with solutions for pancreatic cancer as soon as possible. There are several types of pancreatic cancer, but pancreatic ductal adenocarcinoma (PDA) claims a whopping 90% of all pancreatic cancer diagnoses. PDA claims a dismal five-year survival rate, which is at 12% – the lowest such figure for any type of cancer.  

Furthermore, there are approximately 460,000 people worldwide and 64,000 people in the U.S. who are diagnosed with pancreatic cancer annually. It is the third most commonly diagnosed cancer in the U.S. Its prevalence and dire nature make it a unique and harrowing form of cancer. 

The only currently viable solution for curing a patient of pancreatic cancer is the removal of the pancreas itself. Yet, fewer than one in five patients are eligible for the procedure, and it frequently leads to relapses. However, immunotherapy holds the potential for improving pancreatic cancer patient outcomes, specifically with multiple ongoing clinical trials. Additionally, there are two checkpoint inhibitors – a type of immunomodulator treatment that block immune checkpoints that tumors opportunistically manipulate to shut down the body’s natural immune response – that have earned U.S. FDA approval as immunotherapy treatments for prostate cancer. Dostarlimab is approved for patients with later-stage pancreatic cancer with DNA mismatch repair deficiency (dMMR). Another immunotherapy drug, Pembrolizumab can be treated in patients with high microsatellite instability (MSI-H), dMMR, or high tumor mutational burden (TMB-H). 

CRI’s Impact on Combating Pancreatic Cancer 

Immunologists are working tirelessly to help patients with pancreatic cancer and to ensure a tomorrow where it simply does not exist. CRI is proud to be funding several such immunologists and has been doing so for decades. CRI Scientific Advisory Council Associate Director Elizabeth Jaffee, MD (Johns Hopkins University) and former CRI predoctoral fellow Eric Lutz, PhD (Johns Hopkins University) discovered that the GVAX vaccine could enable the immune system to detect non-immunogenic pancreatic tumors more easily. 

“It takes decades and decades of understanding a disease before you can develop new therapies,” says Dr. Jaffee. “CRI has been there for all of us: for patients, for researchers, for the entire community. The Cancer Research Institute likes the challenge of taking on really bad diseases that nobody else will. It will help make sure the immune system can fight all cancers, not just a few.” 

CRI Postdoctoral Fellow Dr. Zebin Xiao, PhD (University of Pennsylvania), is one of several scientists CRI currently funds with a specific focus on pancreatic cancer. His work focuses on the tumor microenvironment of solid tumors. He is using CAR-T cells to target cancer associated fibroblasts in desmoplastic pancreatic tumors. By depleting these fibroblasts, he was able to tame these highly treatment resistant tumors and make them responsive to the second round of immunotherapy.   

“We are treating established desmoplastic pancreatic tumors with CAR T cells directed to fibroblast activation protein (FAP)” says Dr. Xiao. He further explains, “Depletion of FAP+CAFs results in loss of the structural integrity of desmoplastic matrix. This renders these highly treatment-resistant cancers susceptible to subsequent treatment with a tumor antigen (mesothelin)-targeted CAR T cells and to anti-PD-1 antibody therapy.” 

Clinical Trials Could Help Neutralize Pancreatic Cancer 

Recently, CRI Scientific Advisory Council member Robert Vonderheide, MD, DPhil (University of Pennsylvania) led a clinical trial with a promising approach – targeting the CD40 pathway using both checkpoint immunotherapy and chemotherapy for patients with previously untreated metastatic pancreatic cancer.  The analysis of biosignatures could serve as an initial step towards personalized approach to determine intervention that could benefit most from specific chemo-immunotherapy therapies, this could illuminate clearer treatment plans and more positive outcomes specifically regarding immunotherapy for pancreatic cancer patients. “For patients with pancreatic cancer, we are activating the immune system in a way we have not before, and we are doing that selectively. Novel combinations of chemotherapy and immunotherapy may work together to offer benefit for patients with pancreatic cancer. This partnership will deliver bold, science-driven ideas, and advance clinical trials as the research progresses,” says Dr. Vonderheide. 

Following the initial clinical trial, CRI has recommitted its efforts to combating pancreatic cancer by linking with the Lustgarten Foundation on the REVOLUTION clinical trial to bolster chemo-immunotherapy outcomes for pancreatic cancer patients. The partnership for this trial, dubbed INSPIRE (Integrated Network for Supporting Pancreatic Cancer Immunotherapy Research Efforts), demonstrates a shared purpose between CRI and the Lustgarten Foundation to accelerate progress in immunotherapy research for pancreatic cancer to make the disease curable. A unique aspect of the trial is its malleability, wherein immunologists can test multiple hypotheses and build upon these learnings to help produce optimal research outcomes. 

There is a long way to go in the fight against cancer, particularly with pancreatic cancer. The focus and determination of CRI scientists like Drs. Jaffee, Vonderheide, and Xiao, partnered with your support, goes a long way towards producing improved outcomes for pancreatic cancer patients and creating a world immune to cancer. 

Do you want to do something big for pancreatic cancer? Make a donation to the Cancer Research Institute today.

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